The NR2B subunit in NMDA receptors is functionally important during cerebellar granule cell migration

VEGF modulates NMDA receptors activity in cerebellar granule cells through Src-family kinases before synapse formation

“…During postnatal cerebellar development, migrating GCs predominantly express the NR2B subunit (19), and, when blocked, GC migration is impaired (12). Further evidence that NMDARs regulate GC migration is provided by findings that GC migration is inhibited by NMDAR blockade and accelerated by enhanced NMDAR activity (11,13).…”

“…Prompted by the link between VEGF and NMDAR, we assessed whether Flk1 associates with NMDARs in GCs. During cerebellar development, Flk1 and NR2B are expressed in migrating GCs and are needed for GC migration (2,12,13). Both molecules were found to be coexpressed by GCs ] i by αFlk1 but not by control IgG (n = 44, ***P < 0.001 for IgG; n = 50, P = not significant for αFlk1).…”

“…Interestingly, before neurons establish synapses, activation of NMDARs results in Ca 2+ influx ([Ca 2+ ] i ), which promotes, among other processes, proliferation and survival of neuroblasts (6,7), filopodia formation and growth cone turning (8,9), and migration of cortical and cerebellar neurons (10)(11)(12)(13). In general, NMDARs have been less extensively studied before synapse formation than at developing or established synapses (14)(15)(16).…”

Nurr1 Protein Is Required for N-Methyl-d-aspartic Acid (NMDA) Receptor-mediated Neuronal Survival

“…During its migration, they need glutamatergic stimulation from the mossy fibers. The stimulation of NMDAR is necessary for the maintenance of these neurons during cerebellum development (7)(8)(9). Failure to receive mossy fiber inputs will drive CGCs to apoptotic death (10,11).…”

Methylmercury-Dependent Increases in Fluo4 Fluorescence in Neonatal Rat Cerebellar Slices Depend on Granule Cell Migrational Stage and GABAA Receptor Modulation

“…Rats and mice are also susceptible to MeHg during a postnatal period of CGC migration, suggesting it is not the time before or after birth that determines susceptibility, but rather some mechanism involved in neuronal migration and survival (Rice and Barone, 2000;Sakamoto et al, 2004). CGC migration has been studied extensively in isolated acutely prepared slices (Komuro and Rakic, 1995), as well as organotypic slice culture (Komuro and Rakic, 1995;Kunimoto and Suzuki, 1997;Mancini and Atchison, 2007). CGC migration depends on transient increases in intracellular calcium concentration ([Ca 21 ] i ) (Komuro and Rakic, 1998;Komuro and Kumada, 2005), which, in turn, are modulated by N-type (Cav2.2) voltage-gated Ca 21 channels (VGCCs) (Komuro and Rakic, 1992), N-methyl-D-aspartate (NMDA) receptors (Komuro and Rakic, 1993), and intracellular signaling pathways (Komuro and Rakic, 1995;Komuro et al, 2015).…”